In allergic, autoimmune and other diseases associated with abnormalities of the immunological function, and diseases accompanied by abnormalities of the function, a derangement of the balance of T cell subsets is frequently found and it is being made increasingly clear that this derangement has much to do with the onset and exacerbation of those diseases [Annual Review of Immunology, 12, 227-257 (1994); Trends in Pharmacological Science, 15, 324-332 (1994), Immunology Today, 16, 34-38 (1995), ditto, 17, 138-146 (1996)]. However, there is not known a therapeutic drug that exhibits efficacy in such diseases through positive correction of the balance of T cell subsets.
Meanwhile, in the field of organ transplantation, it is known that T helper-1 cells play a central role in graft rejection. However, there is not known a drug that would contribute to an increased survival of grafts or prevent graft-vs.-host diseases due to transplanted myelocytes by selective modulation of the functions of T cell subsets.
A monocyclic 1,4-thiazine compound having antiallergic activity is disclosed in JP-A 275869/1990. A tricyclic 1,4-thiazine derivative having antiallergic activity is described in Chemical and Industry, 3, 227-228 (1989). JP-A 275870/1990 describes an antiallergic bicyclic 1,4-thiazine derivative.
Aside from them, several other bicyclic 1,4-thiazine derivatives are described in Journal of Chemical Society Chemistry Communication, 19, 1394-1395 (1992), Heterocycles, 27(10), 2297-2300 (1988), and Synthesis, 6, 481-482 (1983).
Recent years have seen an increased incidence of allergic, autoimmune, and other diseases associated with immunological abnormalities, and diseases accompanied by such immunological abnormalities and this is presenting a serious problem in medical care today. This category of illness encompasses a broad spectrum of diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, malignant anemia, ideopathic thrombocytopenic purpura, severe myasthenia, scleroderma, uveitis, Hashimoto's disease, Sjogren's disease, Addison's disease, Basedow's disease, granulocytopenia, bronchial asthma, allergic rhinitis, atopic dermatitis, pollinosis, contact dermatitis, hypersensitivity pneumonitis, lupus nephritis, inflammatory bowel disease, chronic obstructive pulmonary disease, and psoriasis, among others. Recently, the abnormality of the balance of T cell subsets as found in these diseases has gathered attention and, in particular, it is conjectured today that a marked bias in favor of T helper-1 cells or helper-2 cells is a major factor in the onset and exacerbation of such diseases. For the treatment of these diseases, a variety of drugs including steroids, nonsteroidal antiinflammatory drugs, and antihistaminics have been employed but no satisfactory efficacy has been obtained to this day.
Moreover, in the field of organ transplantation, it is known, as mentioned above, that T helper-1 cells play a cardinal role in graft rejection. In this field, steroids, cytotoxic agents, cyclosporins, and tacrolimus, among others, are being used for increasing the survival of grafts or preventing graft-vs-host diseases due to transplanted myelocytes but the adverse reactions associated with the use of these drugs, such as renal impairment and liver damage, are presenting problems today.